The Pavlovian conditioning situation is defined by a set of operations in which the conditional stimulus is paired a number of times with an unconditional stimulus. As suggested by Pavlov, the usual drug administration procedure is similar to this paradigm, with the conditional stimulus constituting those environmental stimuli which regularly precede the pharmacological stimulation. Recent research suggests that the effects of a drug are modulated by conditional drug responses elicited by predrug stimuli. According to a model of morphine tolerance based on this research, drug-compensatory conditional responses, evidenced in anticipation of the pharmacological stimulation, attenuate the drug effect and contribute to tolerance. This model may be contrasted with alternative formulations of tolerance which do not acknowledge any role for associative processes. The major objectives of the research proposed in this application are to evaluate unique predictions of this model of tolerance. In addition, experiments are proposed to examine the model's applicability to opiate effects commonly (but, apparently, frequently erroneously) attributable to "overdose", and to evaluate the relationship between the conditioning theory of tolerance and a conditioning analysis of opiate dependence. Rats are used as subjects in all the proposed research. In various experiments, the effects of morphine will be determined by measuring the analgesic, thermal, and/or behavioral effects of the opiate. As time permits, additional research will examine the relevance of learning processes to tolerance to nonopiate drugs, and also to drug sensitization.